Mesenchymal Stem Cell-Based Therapy for Kidney Disease: A Review of Clinical Evidence
Table 1
Current clinical trials conducted worldwide using MSC to treat kidney diseases, from the US National Institute of Health database (ClinicalTrials.gov).
A controlled trial of allogeneic mesenchymal stem cells for the treatment of refractory lupus
Los Angeles, California; Atlanta, Georgia; Chicago, Illinois; Rochester, New York; Chapel Hill, North Carolina; Charleston, South Carolina, United States
II
Systemic lupus erythematosus
Clinical response defined by the SLE responder index
Change in SLEDAI score, renal and nonrenal organ system flares
12 months
81
Allogeneic ucMSC
Experimental 1: single MSC i.v. infusion MSC Experimental 2: single MSC i.v. infusion MSC Placebo comparator: only vehicle
Mesenchymal stem cell transplantation in the treatment of chronic allograft nephropathy
Fuzhou, Fujian, China
I/II
Kidney transplant, chronic allograft nephropathy
Renal function (sCr and Cr clearance rate)
Patient and graft survival, the proportion of renal biopsy, the incidence of infectious complications Incidence of adverse events associated with MSC and immunosuppression
12 months
20
Allogeneic MSC
Experimental 1: MSC infusion and full immunosuppressive therapy Placebo comparator: full immunosuppressive therapy
Experimental: two doses of autologous MSC infusion, one day before transplant and 30 days after transplant Active comparator: two doses allogeneic MSC infusion one day before transplant and 30 days after transplant Placebo comparator: only vehicle
Incidence of slow graft function, incidence of delayed graft function, proportion of normal renal function recovery, time to renal function recovery, patient survival, renal graft survival, incidence of acute rejection, severe adverse events
12 months
120
Allogeneic bmMSC
Experimental: four doses of MSC i.v. infusion at days 0, 7, 14, 21 after renal artery reperfusion and induction therapy Placebo comparator: only vehicle at days 0, 7, 14, 21 and induction therapy
Mesenchymal stem cells after renal or liver transplantation
Liège, Belgium
I/II
Kidney failure
Safety (MSC infusion toxicity), incidence of infections and cancers
Patient and graft survivals, feasibility and safety, effects of MSC on graft function, rejection rates, recipient's immune function, development of anti-MSC donor HLA antibodies
Induction therapy with autologous mesenchymal stem cells for kidney allografts
Fuzhou, Fujian, China
Renal transplant rejection
Incidence of acute rejection and early renal function recovery
Patient and graft survival and prevalence of adverse events
12 months
165
Autologous bmMSC
Active comparator 1: two infusions of MSC, one at releasing renal artery clamp and one two weeks after transplantation and regular immunosuppressive agents Active comparator 2: two infusions of MSC, one at releasing renal artery clamp and one two weeks after transplantation and immunosuppressive agents with 80% less calcineurin inhibitor Active comparator 3: anti-interleukin 2 receptor antibody and regular immunosuppressive agents
Proportion of normal renal function recovery, time to renal function recovery, acute rejection rate, patient and graft survival rate, incidence of severe adverse events
12 months
120
Allogeneic bmMSC
Experimental: four i.v. administration doses of MSC every week Placebo comparator: only vehicle every week
A perspective multicenter controlled study on application of mesenchymal stem cell (MSC) to prevent rejection after renal transplantation by donation after cardiac death
Guangzhou, Guangdong, China
I
Disorder related to renal transplantation, renal transplant rejection
Safety (Incident rates of BPAR and DGF)
12 months
260
bmMSC
Experimental 1: routine treatment protocol plus MSC i.v. /Kg 48 hours before operation Placebo comparator 1: routine treatment protocol Experimental 2: routine treatment protocol plus MSC i.v. /Kg plus MSC i.a. /Kg 48 hours before operation Placebo comparator 2: routine treatment protocol Experimental 3: routine CMR treatment protocol plus MSC i.v. /Kg at days 1, 7 Placebo comparator 3: routine CMR treatment protocol Experimental 4: routine AMR treatment protocol plus MSC i.v. /Kg at days 1, 7 Placebo comparator 4: routine AMR treatment protocol
Mesenchymal stem cells under Basiliximab/low dose RATG to induce renal transplant tolerance
Bergamo, Italy
Kidney transplant
Inhibition of memory T-cell response and/or naive T-cell response, Induction of donor-reactive T-cell anergy and the appearance in the peripheral blood of regulatory T-cells
Safety of MSC infusion, graft function, graft rejection
12 months
4
Syngeneic bmMSC
Experimental: MSC infusion /Kg at the time of kidney transplant plus induction and maintenance therapy Active Comparator: immunosuppressive therapy plus induction and maintenance therapy
Allogeneic mesenchymal stromal cell therapy in renal transplant recipients
Leiden, Netherlands
I
Rejection, graft loss
Biopsy proven acute rejection/graft loss
Comparison of fibrosis by quantitative Sirius Red scoring, serious adverse events, renal function measured by eGFR (MDRD formula) and iohexol clearance, CMV, BK infection (viremia, disease, and syndrome; and subtypes of BK viremia) and other opportunistic infections, development of de novo DSA and immunological responses
12 months
10
Allogeneic bmMSC
Experimental: two i.v. MSC infusions 1-/Kg at weeks 25, 26 after transplantation
Mesenchymal stromal cells in kidney transplant recipients
Bergamo, Italy
I
Kidney transplant rejection
Naive and memory T-cell count (CD45RA/CD45RO), T-cell function (ELISPOT assay), number of adverse events, regulatory T-cell count, urinary FOXP3 mRNA expression (RT qPCR)
12 months
6
Autologous bmMSC
Experimental: single i.v. MSC infusion /Kg the day before the kidney transplant procedure
Mesenchymal stromal cell therapy in renal recipients
Leiden, Netherlands
II
Renal transplant rejection, fibrosis
Histology (fibrosis evaluation by Sirius Red)
Renal function and proteinuria, number of participants with CMV and BK infection and other opportunistic infections between groups, number of participants with adverse events, composite, end point efficacy failure, presence of donor specific antibodies and immunologic monitoring
6 months
70
Autologous bmMSC
Experimental: three i.v. MSC infusions 1-/Kg 7 days apart, 6 and 7 weeks after transplantation plus Everolimus administration Placebo comparator: tacrolimus plus Everolimus administration
